16-69726719-G-C

Variant names:

• chr16-69726719-G-C
• rs689459
• ENST00000690354.2:n.109G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690354.2(NQO1-DT):​n.109G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 400,226 control chromosomes in the GnomAD database, including 604 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.044 (495 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (109 hom.)
• Consequence: NQO1-DT ENST00000690354.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 7 publications found

Genes affected

NQO1-DT (HGNC:55344): (NQO1 divergent transcript)

NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000690354.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1	NM_000903.3	MANE Select	c.-280C>G		upstream_gene	N/A	NP_000894.1
	NQO1	NM_001025433.2		c.-280C>G		upstream_gene	N/A	NP_001020604.1
	NQO1	NM_001025434.2		c.-280C>G		upstream_gene	N/A	NP_001020605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO1-DT	ENST00000690354.2		n.109G>C		non_coding_transcript_exon	Exon 1 of 2
	NQO1	ENST00000320623.10	TSL:1 MANE Select	c.-280C>G		upstream_gene	N/A	ENSP00000319788.5
	NQO1	ENST00000564043.1	TSL:1	c.-275C>G		upstream_gene	N/A	ENSP00000455020.1

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6618 AN: 151992 Hom.: 497 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0317

GnomAD4 exome AF: 0.00577 AC: 1432 AN: 248116 Hom.: 109 Cov.: 2 AF XY: 0.00497 AC XY: 639 AN XY: 128638

African (AFR) AF: 0.151 AC: 1089 AN: 7204

American (AMR) AF: 0.00707 AC: 62 AN: 8766

Ashkenazi Jewish (ASJ) AF: 0.000112 AC: 1 AN: 8904

East Asian (EAS) AF: 0.00 AC: 0 AN: 21220

South Asian (SAS) AF: 0.0000992 AC: 1 AN: 10078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19134

Middle Eastern (MID) AF: 0.00500 AC: 6 AN: 1200

European-Non Finnish (NFE) AF: 0.000301 AC: 47 AN: 155894

Other (OTH) AF: 0.0144 AC: 226 AN: 15716

GnomAD4 genome AF: 0.0435 AC: 6618 AN: 152110 Hom.: 495 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74372

African (AFR) AF: 0.152 AC: 6304 AN: 41426

American (AMR) AF: 0.0144 AC: 220 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68024

Other (OTH) AF: 0.0314 AC: 66 AN: 2104

Alfa AF: 0.0327 Hom.: 32

Bravo AF: 0.0488

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		-0.12
PromoterAI		-0.28	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs689459; hg19: chr16-69760622;